蛋白质折叠是一个复杂的,以重分子和细胞足迹为特征的多系统过程。分子伴侣机制能够实现适当的蛋白质折叠和稳定的构象。与蛋白质折叠过程相伴的其他途径包括转录,翻译,翻译后修饰,通过泛素-蛋白酶体系统降解,和自噬。因此,折叠过程可能以几种不同的方式出错。大多数神经退行性疾病背后的致病基础是任何水平的蛋白质稳态(即蛋白质稳态)的破坏将最终导致蛋白质错误折叠。错误折叠的蛋白质通常聚集并积累以通过细胞应激途径引发神经毒性并因此引起神经退行性疾病。疾病的表现通常取决于神经毒性影响的特定大脑区域。神经退行性疾病与年龄有关,随着人类继续延长寿命和追求更长的预期寿命,它们的发病率预计会上升。我们目前回顾了蛋白质错误折叠和聚集的后遗症,以及这些现象在包括阿尔茨海默病在内的几种神经退行性疾病中的作用,亨廷顿病,肌萎缩侧索硬化,帕金森病,传染性海绵状脑病,和脊髓小脑共济失调.治疗和治疗的策略也被赋予了关于损害,抑制,或逆转蛋白质的错误折叠。
Protein folding is a complex, multisystem process characterized by heavy molecular and cellular footprints. Chaperone machinery enables proper protein folding and stable conformation. Other pathways concomitant with the protein folding process include transcription, translation, post-translational modifications, degradation through the ubiquitin-proteasome system, and autophagy. As such, the folding process can go awry in several different ways. The pathogenic basis behind most neurodegenerative diseases is that the disruption of protein homeostasis (i.e. proteostasis) at any level will eventually lead to protein misfolding. Misfolded proteins often aggregate and accumulate to trigger neurotoxicity through cellular stress pathways and consequently cause neurodegenerative diseases. The manifestation of a disease is usually dependent on the specific brain region that the neurotoxicity affects. Neurodegenerative diseases are age-associated, and their incidence is expected to rise as humans continue to live longer and pursue a greater life expectancy. We presently
review the sequelae of protein misfolding and aggregation, as well as the role of these phenomena in several neurodegenerative diseases including Alzheimer\'s disease, Huntington\'s disease, amyotrophic lateral sclerosis, Parkinson\'s disease, transmissible spongiform encephalopathies, and spinocerebellar ataxia. Strategies for treatment and therapy are also conferred with respect to impairing, inhibiting, or reversing protein misfolding.